Lipid membranes accelerate amyloid formation in the mouse model of AA amyloidosis

Introduction: AA amyloidosis develops as a result of prolonged inflammation and is characterized by deposits of N-terminal proteolytic fragments of the acute phase reactant serum amyloid A (SAA). Macrophages are usually found adjacent to amyloid, suggesting their involvement in the formation and/or degradation of the amyloid fibrils. Furthermore, accumulating evidence suggests that lipid membranes accelerate the fibrillation of different amyloid proteins.

Methods: Using an experimental mouse model of AA amyloidosis, we compared the amyloidogenic effect of liposomes and/or amyloid-enhancing factor (AEF). Inflammation was induced by subcutaneous injection of silver nitrate followed by intravenous injection of liposomes and/or AEF to accelerate amyloid formation.

Results: We showed that liposomes accelerate amyloid formation in inflamed mice, but the amyloidogenic effect of liposomes was weaker compared with AEF. Regardless of the induction method, amyloid deposits were mainly found in the marginal zones of the spleen and coincided with the depletion of marginal zone macrophages, while red pulp macrophages and metallophilic marginal zone macrophages proved insensitive to amyloid deposition.

Conclusions: We conclude that increased intracellular lipid content facilitates AA amyloid fibril formation and show that the mouse model of AA amyloidosis is a suitable system for further mechanistic studies.     

Tuberculosis Disease Diagnosis Using Artificial Immune Recognition System

Background: There is a high risk of tuberculosis (TB) disease diagnosis among conventional methods.Objectives:This study is aimed at diagnosing TB using hybrid machine learning approaches.Materials and Methods: Patient epicrisis reports obtained from the Pasteur Laboratory in the north of Iran were used. All 175 samples have twenty features. The features are classified based on incorporating a fuzzy logic controller and artificial immune recognition system. The features are normalized through a fuzzy rule based on a labeling system. The labeled features are categorized into normal and tuberculosis classes using the Artificial Immune Recognition Algorithm.Results:Overall, the highest classification accuracy reached was for the 0.8 learning rate (α) values. The artificial immune recognition system (AIRS) classification approaches using fuzzy logic also yielded better diagnosis results in terms of detection accuracy compared to other empirical methods. Classification accuracy was 99.14%, sensitivity 87.00%, and specificity 86.12%.     

COVID-19-associated stroke risk: Could nutrition and dietary patterns have a contributing role?

The novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 has created a life-threatening world pandemic. Unfortunately, this disease can be worse in older patients or individuals with comorbidities, having dangerous consequences, including stroke. COVID-19–associated stroke widely increases the risk of death from COVID-19. In addition to the personal hygiene protocols and preventive policies, it has been proven that immune-compromised, oxidative, and pro-coagulant conditions make a person more susceptible to severe COVID-19 complications, such as stroke; one of the most effective and modifiable risk factors is poor nutritional status. Previous literature has shown that healthy dietary patterns, such as the Mediterranean diet, some food groups, and specific micronutrients, reduce the risk of ischemic and hemorrhagic stroke. In this work, for the first time, we hypothesized that a healthy diet could also be a protective/preventive factor against COVID-19–associated stroke risk. In order to prove this hypothesis, it is required to study nutritional intake and dietary patterns in patients suffering from COVID-19–associated stroke. If this hypothesis is proven, the chronic supportive role of a healthy diet in critical situations will be highlighted once again.     

Phase II trial of sequential high-dose chemotherapy with paclitaxel,melphalan and cyclophosphamide,thiotepa and carboplatin with peripheral blood progenitor support in women with responding metastatic breast cancer

A single high-dose cycle of chemotherapy can produce response rates in excess of 50%. However, disease-free survival (DFS) is 15-20% at 5 years. The single most important predictor of prolonged DFS is achieving a complete response (CR). Increasing the proportion of patients who achieve a complete response may improve disease-free survival. Women with metastatic breast cancer and at least a partial response (PR) to induction chemotherapy received three separate high-dose cycles of chemotherapy with peripheral blood progenitor support and G-CSF. The first intensification was paclitaxel (825 mg/m(2)), the second melphalan (180 mg/m(2)) and the third consisted of cyclophosphamide 6000 mg/m(2) (1500 mg/m(2)/day x 4), thiotepa 500 mg/m(2) (125 mg/m(2)/day x 4) and carboplatin 800 mg/m(2) (200 mg/m(2)/day x 4) (CTCb). Sixty-one women were enrolled and 60 completed all three cycles. Following the paclitaxel infusion most patients developed a reversible, predominantly sensory polyneuropathy. Of the 30 patients with measurable disease, 12 converted to CR, nine converted to a PR*, and five had a further PR, giving an overall response rate of 87%. The toxic death rate was 5%. No patient progressed on study. Thirty percent are progression-free with a median follow-up of 31 months (range 1-43 months) and overall survival is 61%. Three sequential high-dose cycles of chemotherapy are feasible and resulted in a high response rate. The challenge continues to be maintenance of response and provides the opportunity to evaluate strategies for eliminating minimal residual disease.     

Prevention of chemotherapy and radiation toxicity with glutamine

GOALS OF THE WORK: Malignancy produces a state of physiologic stress that is characterized by a relative deficiency of glutamine, a condition that is further exacerbated by the effects of cancer treatment. Glutamine deficiency may impact on normal tissue tolerance to antitumor treatment, and may lead to dose reductions and compromised treatment outcome. Providing supplemental glutamine during cancer treatment has the potential to abrogate treatment-related toxicity. We reviewed the available data on the use of glutamine to decrease the incidence and severity of adverse effects due to chemotherapy and/or radiation in cancer patients. METHODS: We performed a search of the MEDLINE database during the time period 1980-2003, and reviewed the English language literature of both human and animal studies pertaining to the use of glutamine in subjects with cancer. We also manually searched the bibliographies of published articles for relevant references. MAIN RESULTS: The available evidence suggests that glutamine supplementation may decrease the incidence and/or severity of chemotherapy-associated mucositis, irinotecan-associated diarrhea, paclitaxel-induced neuropathy, hepatic veno-occlusive disease in the setting of high dose chemotherapy and stem cell transplantation, and the cardiotoxicity that accompanies anthracycline use. Oral glutamine supplementation may enhance the therapeutic index by protecting normal tissues from, and sensitizing tumor cells to chemotherapy and radiation-related injury. CONCLUSIONS: The role of glutamine in the prevention of chemotherapy and radiation-induced toxicity is evolving. Glutamine supplementation is inexpensive and it may reduce the incidence of gastrointestinal, neurologic, and possibly cardiac complications of cancer therapy. Further studies, particularly placebo-controlled phase III trials, are needed to define its role in chemotherapy-induced toxicity.     

Erythema nodosum secondary to aromatase inhibitor use in breast cancer patients: case reports and review of the literature

Aromatase inhibitors (AI’s) are increasingly being incorporated in the treatment strategy for hormone receptor positive breast cancer either alone or in combination with chemotherapy, biologics in both the adjuvant and metastatic setting [1]. They markedly suppress plasma estrogen levels by inhibiting or inactivating aromatase, the enzyme responsible for the synthesis of estrogens from androgenic substrates [1]. Currently, the three selective aromatase inhibitors that are available are anastrozole, letrozole and exemestane which reduce circulating estrogen to 1 to 10% of pretreatment levels [2]. For advanced breast cancer, aromatase inhibitors appear to be at a minimum, equivalent and perhaps even better than tamoxifen in the first line setting [3, 4]. In primary breast cancer, adjuvant therapy with anastrozole or letrozole appears to be superior to tamoxifen in reducing the risk of relapse [5, 6]. Common adverse effects associated with AI’s include arthralgias (21%), myalgias (12%), other musculoskeletal disorders (28%) and an up to 60% increased risk of bone fracture [7, 8]. However, anastrozole, exemestane and letrozole are associated with significantly fewer endometrial cancers, as well as venous and arterial vascular events, when compared with tamoxifen [9, 10]. Very rarely letrozole and anastrozole can cause a skin rash; the frequency of its occurrence has not been quantified^. However, exemestane has not been reported to cause a skin rash [11]. To date, erythema nodosum (EN) has not been reported as a dermatologic side effect of AI’s. Here, we report three cases of EN which developed in postmenopausal breast cancer patients on AI’s.